Crosstalk between platelets and red blood cells promotes abdominal aortic aneurysm formation and progression

Introduction: Abdominal aortic aneurysm (AAA) represents a cardiovascular disease with high morbidity and mortality. Recent clinical trials revealed no beneficial effects by administering potential growth restrictors; thus, no therapeutic approach is available to date [ 1 ]. Certain factors have been shown to increase the risk for AAA development, e.g. age, smoking, high blood pressure and vascular inflammation [ 2 ]. Thereby, 70-80% of all AAA patients reveal a platelet-rich intraluminal thrombus (ILT) that might be relevant for AAA progression [ 3 ] [ 4 ]. The interaction of platelets and red blood cells (RBCs) is important for thrombus formation in hemostasis and thrombosis. However, the impact of platelets and RBCs in AAA progression and the consequences for ILT formation are poorly understood. Method: Flow cytometric analysis was performed with whole blood from AAA patients. Histological sections of the ILT and the aortic wall were stained with specific markers for RBCs, platelets and thrombospondin-1 (TSP-1). Plasma levels of TSP-1 and CD36 were determined in AAA patients. Results: The flow cytometric analysis of platelets form AAA patients revealed a hyperreactive activation profile, indicated by enhanced integrin a IIb β 3 activation and P-selectin exposure. In addition, increased phosphatidylserine (PS) exposure at the membrane of platelets and RBCs from AAA patients revealed enhanced pro-coagulant activity of these cells compared to age-matched healthy controls (AMCs) as well as carotid artery stenosis patients (ACI). As a first interaction marker of platelets and RBCs relevant for AAA pathology, increased binding of TSP-1 to the platelet surface as well as elevated externalization of CD36 on the RBC surface was detected using flow cytometric analysis of whole blood samples from AAA patients. Furthermore, platelet-RBC conjugates in the circulation were significantly increased in AAA patients compared to AMCs. In line, histological sections of the ILT and the aortic wall were stained with specific markers for platelets, RBCs and TSP-1 indicating an accumulation of TSP-1 and platelet-RBC conjugates in these tissues. Furthermore, plasma concentrations of TSP‑1 and CD36 were found to be significantly increased in AAA patients compared to AMCs. Conclusion: Taken together,platelets showed a pre-activated state in AAA disease. Enhanced PS on the platelet and RBCs surface, as well as increased CD36 on RBCs and TSP‑1 binding to platelets suggest that these disease-specific features might play a crucial role in AAA progression. Publication History Article published online: 13 February 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany